The objective of the proposed studies is to investigate and characterize some of the factors that play a role in determining the reversibility of ischemic damage following myocardial infarction. We plan to produce infarction in the dog under both conscious and anesthetized conditions, excise the heart at various intervals following the onset of ischemia (or reperfusion) and prepare isolated myocytes from a control portion of the left ventricle, from a periinfarcted area, and from the center of the infarction. The novelty of the approach employed in this proposal is the investigation of the interaction of various hormones with their receptors in the isolated myocytes obtained from the above mentioned three locations and to correlate the changes observed in hormone-receptor interaction with the metabolic behavior of the isolated cells as well as the morphologic and ultrastructural appearance of the myocytes. Specifically, beta and alpha adrenergic agonists will be studied along with glucagon insulin and estrogens. The hormone-receptor interaction in the case of catecholamines and insulin is especially of interest because of the known influence of these hormones on the heart (metabolism and mechanics) and on the development of infarct size following coronary artery obstruction. Our preliminary data indicate that both infarcted and periinfarcted areas exhibit alterations in cell membrane properties which are manifested by changes in hormone-receptor interaction, substrate utilization and the morphologic and structural appearance of the cells. Once these changes are characterized, attention will be focused on the reversibility of the alterations and on correlating reversibility with the changed properties of the damaged membranes.